The invention relates to an arrangement for taking up liquid analytes. Such an arrangement has a microtitre plate with a plurality of wells for taking up an analyte.
Such a microtitre plate is used, for example, for a wide variety of applications in medicine and biotechnology for taking up liquids to be analyzed, for example in the field of DNA analysis.
Usually, a different analyte to be analyzed is introduced in each well and via a pipette, usually via a plurality of adjacently arranged elements designed as a so-called pipette comb, the analyte is taken up; in a pipette comb, for example, a respective pipette is provided for each well in a row of the microtitre plate, which has wells arranged in an array.
By means of a pipette, an analyte is in each case withdrawn because of a reduced pressure created in the pipette, i.e., it is sucked up, from the corresponding well which is filled with the analyte and into which the pipette is dipped.
According to a known arrangement, the pipette is in each case coupled, via tubing, to a pump which is assigned uniquely to the respective pipette, and which produces the reduced pressure, in such a way that the analyte can be aspirated through the corresponding pipette by means of the pump and correspondingly can in turn be introduced into the well while being controlled by the pump.
Such a known microtitre plate has, for example, 96 wells with a size of 8 cm×12 cm.
Such a known microtitre plate, however, may in principle have any desired number of wells, usually up to 384.
A particular disadvantage of this known arrangement is that, because of the high number of pumps, it is impractical or sometimes impossible to provide a separate pump on such a small area of 8 cm×12 cm for each well in a row, i.e., for each of such a large number of pipettes.
The production of such a pipette comb, and hence of such an arrangement for taking up liquid analytes, is therefore very demanding and expensive.
It should furthermore be pointed out that, in the this known arrangement, a peristaltic pump is normally used in each case for aspirating the analyte out of the well in question and for introducing it therein.
A considerable disadvantage of this known arrangement is furthermore that a minimum amount of an analyte to be analyzed, of the order of 1 ml, is needed for the analysis.
Another disadvantage is that the large number of pumps required, with the associated tubing arrangement, is very complicated and therefore susceptible to faults.
Furthermore, U.S. Pat. Nos. 5,843,767 and 6,893,816, incorporated herein by reference, describe a Flow-Thru Chip™, by means of which analysis of the analyte with respect to the existence of biological material in the analyte is performed.
The Flow-Thru Chip™, which is a configuration of an analysis chip, has a plurality of channels through which the analyte is fed through the analysis chip, the surface of the channels being provided respectively with probe molecules, generally with molecules which can bind, preferably covalently, the correspondingly targeted biological material whose existence in the analyte is to be detected.
If the biological material in the analyte is a DNA strand with a predefined DNA sequence to be determined, then DNA probe molecules with a sequence complementary to the DNA sequence to be determined are applied to the surface of such a liquid channel in the Flow-Thru Chip™.
If the DNA material with the targeted DNA sequence is present in the analyte, then the DNA strands bind with the corresponding DNA probe molecules of opposite, i.e., complementary sequence.
In general, such an analysis chip is often used for the analysis, i.e., for the detection of macromolecular biopolymers, examples of which include proteins or peptides as well as DNA strands with a respective predefined frequency.
Furthermore, it is well known that it is possible to produce, from glass or silicon, a diaphragm which has a plurality of pores with a constant diameter of from 0.1 μm to 10 μm, and for example, from 0.1 μm to 1 μm.
It is therefore an object of the invention to provide an arrangement for taking up liquid analytes, in which even a large number of wells can be produced and operated in such an arrangement less expensively than is possible with an arrangement according to the prior art.
The object is achieved by the arrangement taking up liquid analytes having the features according to the independent patent claim.
An arrangement for taking up liquid analytes has a microtitre plate with a plurality of wells for taking up an analyte.
In the scope of the invention, a microtitre plate should be understood as being a plate having a plurality of wells for taking up an analyte, which usually have wells which are arranged in an array, i.e., in rows and columns with usually constant distances between them. It should be noted in this context, however, that a microtitre plate is not restricted to such an arrangement, but rather, in the scope of the invention, a microtitre plate should be understood as describing a structure having a plurality of arbitrarily arranged wells for taking up a liquid analyte.
One pipette is provided for a well, and in case of a plurality of wells, a plurality of pipettes are usually provided, a pipette being in each case usable to withdraw an analyte from an associated well, i.e., a well over which the pipette is currently arranged, or to introduce it into this well.
The arrangement has a pump which is coupled to several pipettes in such a way that an analyte can in each case be aspirated through an associated pipette by means of the pump, and analytes can be simultaneously aspirated out of several wells or introduced into several wells by actuating the pump.
In this way, the analytes can be aspirated using a very simple arrangement, in particular a significantly reduced number of pumps compared with the number of wells, for the case in which an analysis chip, for example the Flow-Thru Chip™, with probe molecules applied to the surfaces of the liquid channels, is provided in the suction path, i.e., in the liquid channel inside the pipette, to simultaneously analyze several analytes, which are usually different.
In this way, the overall arrangement can be produced and operated considerably less expensively.
Furthermore, the arrangement is considerably less complex and hence also considerably less prone to problems.
Analysis chips are furthermore provided for analyzing the analyte, one analysis chip being in each case assigned to a well in order to analyze an analyte introduced into the respective well. The surface of at least a part of the analysis chips, which surface comes into contact with the analyte, is designed in such a way the biological material for binding molecules contained in the analyte can be fixed on the surface.
This straightforwardly permits, for the first time, parallel analysis of biological material in a robust but nevertheless inexpensive and fast way.
The pipettes may be configured as a pipette comb.
According to another configuration of the invention, the pipette comb has a first element and a second element, which is coupled to the first element, the second element having the pipettes.
A plate may be arranged between the first element and the second element, the analysis chips for analyzing the analytes being arranged in this plate according to one configuration of the invention. One take-up well for analyzing an analyte introduced into the respective well is in each case usually provided for one analysis chip.
The surface of at least a part of the analysis chips, which surface comes into contact with the analyte, may have biological material so that it is possible to bind biological molecules, for example macromolecular biopolymers, contained in the analyte.
In the scope of this invention, macromolecular biopolymers should be understood as meaning, for example, proteins or peptides as well as DNA molecules.
According to one configuration of the invention, the microtitre plate has 96 wells or 384 wells for taking up a respective analyte.
An elastic diaphragm may in each case be sealingly arranged over at least some of the pipettes, so that the analyte can be sucked out of the corresponding well or introduced into the corresponding well by deforming the diaphragm.
Clearly, this configuration means that, by deforming the diaphragm, a reduced pressure or an overpressure can be produced in the pipette, i.e., between the diaphragm and the analyte in the pipette, it being possible to move the analyte inside the pipette, preferably through the analysis chip.
One advantage, when such a diaphragm is used, is that closed chambers are formed so the analytes cannot give off any vapours which may possibly be toxic to humans.
According to one configuration of the invention, a buffer plate is provided for each pipette, in order to mix the analyte supplied through the pipette, so the analysis result is improved further since, owing to the baffle plate in the flow path of the analyte, the mixing of the analyte and hence the contact of the analyte with the probe molecules on the surface of the liquid channels of the analysis chip is improved further.
Furthermore, according to one configuration of the invention, for the case in which temperature control is required in the arrangement, for example for chemical reactions or biological reactions, measuring elements and heating elements are provided in the arrangement.
These elements may be integrated in the analysis chip according to one configuration of the invention.
According to another configuration of the invention, the pump can be operated in such a way that the analyte is sucked by means of the reduced pressure produced in the pipette, which is less than an analyte surface tension possibly formed in the pipette.
This procedure utilizes the discovery that because of the capillary effect, especially at such small dimensions in a pipette for a microtitre plate, a very strong capillary effect is formed which leads to a very considerable surface tension on the analyte to be taken up, when all of the analyte has been sucked out of the well.
This approach prevents very straightforwardly, without any additional complex control means being required, air or another gas from being sucked into the pipette after all of the analyte has been taken up from the respective well.
This ensures that the amount of analyte, generally liquid and/or gas, which is taken up is always precisely the amount needed for the analysis.
Clearly, the invention consists in the fact that, by providing one pump for several pipettes and configuring them in such a way that different analytes can in each case be sucked simultaneously from several wells by means of one pump, and correspondingly analyzed, the complexity and the costs of an arrangement for taking up liquid analytes is improved considerably.